rs3092910

Variant names:

• chr11-108310190-T-C
• rs3092910
• NM_000051.4:c.5793T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-108310190-T-C
• chr11-108310190-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000051.4(ATM):​c.5793T>C​(p.Ala1931Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00677 in 1,613,558 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A1931A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0060 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0068 (35 hom.)
• Consequence: ATM NM_000051.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:27
• Conservation: PhyloP100: -0.136
• Publications: 21 publications found

Genes affected

ATM (HGNC:795): (ATM serine/threonine kinase) The protein encoded by this gene belongs to the PI3/PI4-kinase family. This protein is an important cell cycle checkpoint kinase that phosphorylates; thus, it functions as a regulator of a wide variety of downstream proteins, including tumor suppressor proteins p53 and BRCA1, checkpoint kinase CHK2, checkpoint proteins RAD17 and RAD9, and DNA repair protein NBS1. This protein and the closely related kinase ATR are thought to be master controllers of cell cycle checkpoint signaling pathways that are required for cell response to DNA damage and for genome stability. Mutations in this gene are associated with ataxia telangiectasia, an autosomal recessive disorder. [provided by RefSeq, Aug 2010]

C11orf65 (HGNC:28519): (chromosome 11 open reading frame 65) Predicted to be involved in negative regulation of mitochondrial fission and negative regulation of protein targeting to mitochondrion. Predicted to be located in cytosol and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 11-108310190-T-C is Benign according to our data. Variant chr11-108310190-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 128459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.136 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00604 (920/152308) while in subpopulation EAS AF = 0.0106 (55/5184). AF 95% confidence interval is 0.00837. There are 6 homozygotes in GnomAd4. There are 421 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000051.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	NM_000051.4	MANE Select	c.5793T>C	p.Ala1931Ala	synonymous	Exon 39 of 63	NP_000042.3
	ATM	NM_001351834.2		c.5793T>C	p.Ala1931Ala	synonymous	Exon 40 of 64	NP_001338763.1	Q13315
	C11orf65	NM_001330368.2		c.641-1119A>G		intron	N/A	NP_001317297.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	ENST00000675843.1	MANE Select	c.5793T>C	p.Ala1931Ala	synonymous	Exon 39 of 63	ENSP00000501606.1	Q13315
	ATM	ENST00000452508.7	TSL:1	c.5793T>C	p.Ala1931Ala	synonymous	Exon 40 of 64	ENSP00000388058.2	Q13315
	ATM	ENST00000527805.6	TSL:1	n.*857T>C		non_coding_transcript_exon	Exon 37 of 61	ENSP00000435747.2	E9PIN0

Frequencies

GnomAD3 genomes AF: 0.00605 AC: 921 AN: 152190 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00789

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00657

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00506 AC: 1271 AN: 251034 AF XY: 0.00488

Gnomad AFR exome AF: 0.00790

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00298

Gnomad EAS exome AF: 0.0114

Gnomad FIN exome AF: 0.000601

Gnomad NFE exome AF: 0.00677

Gnomad OTH exome AF: 0.00458

GnomAD4 exome AF: 0.00685 AC: 10005 AN: 1461250 Hom.: 35 Cov.: 31 AF XY: 0.00664 AC XY: 4825 AN XY: 726946

African (AFR) AF: 0.00768 AC: 257 AN: 33454

American (AMR) AF: 0.00188 AC: 84 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00341 AC: 89 AN: 26114

East Asian (EAS) AF: 0.00702 AC: 278 AN: 39584

South Asian (SAS) AF: 0.00140 AC: 121 AN: 86234

European-Finnish (FIN) AF: 0.000600 AC: 32 AN: 53362

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5760

European-Non Finnish (NFE) AF: 0.00773 AC: 8598 AN: 1111672

Other (OTH) AF: 0.00893 AC: 539 AN: 60362

GnomAD4 genome AF: 0.00604 AC: 920 AN: 152308 Hom.: 6 Cov.: 32 AF XY: 0.00565 AC XY: 421 AN XY: 74484

African (AFR) AF: 0.00789 AC: 328 AN: 41572

American (AMR) AF: 0.00327 AC: 50 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3472

East Asian (EAS) AF: 0.0106 AC: 55 AN: 5184

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4834

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00657 AC: 447 AN: 68012

Other (OTH) AF: 0.00427 AC: 9 AN: 2110

Alfa AF: 0.00552 Hom.: 1

Bravo AF: 0.00634

Asia WGS AF: 0.00927 AC: 32 AN: 3468

EpiCase AF: 0.00698

EpiControl AF: 0.00421

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	8	not specified (8)
-	-	6	not provided (6)
-	-	4	Ataxia-telangiectasia syndrome (4)
-	-	4	Hereditary cancer-predisposing syndrome (4)
-	-	2	Familial cancer of breast (2)
-	-	1	ATM-related disorder (1)
-	-	1	Hereditary breast ovarian cancer syndrome (1)
-	-	1	Malignant tumor of breast (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.9
DANN	Benign	0.85
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3092910; hg19: chr11-108180917;