chr3-169926753-C-T

Variant names:

• chr3-169926753-C-T
• rs748049755
• NM_001304366.2:c.491C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001304366.2(SAMD7):​c.491C>T​(p.Pro164Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000554 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000055 (0 hom.)
• Consequence: SAMD7 NM_001304366.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21
• Publications: 1 publications found

Genes affected

SAMD7 (HGNC:25394): (sterile alpha motif domain containing 7) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in negative regulation of transcription, DNA-templated. Predicted to be located in cytoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SAMD7 Gene-Disease associations (from GenCC):

• macular dystrophy with or without cone dysfunction

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24566379).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304366.2. 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
	SAMD7	NM_001304366.2	MANE Select	c.491C>T	p.Pro164Leu	missense	Exon 6 of 9	NP_001291295.1	Q7Z3H4
	SAMD7	NM_182610.4		c.491C>T	p.Pro164Leu	missense	Exon 6 of 9	NP_872416.1	Q7Z3H4
	SAMD7	NR_130713.2		n.970C>T		non_coding_transcript_exon	Exon 7 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMD7	ENST00000335556.7	TSL:1 MANE Select	c.491C>T	p.Pro164Leu	missense	Exon 6 of 9	ENSP00000334668.3	Q7Z3H4
	SAMD7	ENST00000428432.6	TSL:1	c.491C>T	p.Pro164Leu	missense	Exon 6 of 9	ENSP00000391299.2	Q7Z3H4
	SAMD7	ENST00000487910.1	TSL:1	n.*307C>T		non_coding_transcript_exon	Exon 6 of 9	ENSP00000420460.1	F8WDF1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251412 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000554 AC: 81 AN: 1461890 Hom.: 0 Cov.: 32 AF XY: 0.0000605 AC XY: 44 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000728 AC: 81 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.2
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.23
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.017	D
Polyphen		0.99	D
Vest4		0.31
MutPred		0.51		Loss of disorder (P = 0.0317)
MVP		0.62
MPC		0.57
ClinPred		0.98	D
GERP RS		6.2
Varity_R		0.086
gMVP		0.20
Mutation Taster		=89/11	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: rs748049755; hg19: chr3-169644541;