rs10117507

Variant names:

• chr9-21864099-G-A
• rs10117507
• NM_002451.4:c.*2085G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-21864099-G-A
• chr9-21864099-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002451.4(MTAP):​c.*2085G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 985,148 control chromosomes in the GnomAD database, including 21,816 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4844 hom., cov: 32)
  • Exomes 𝑓: 0.20 (16972 hom.)
• Consequence: MTAP NM_002451.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.681
• Publications: 10 publications found

Genes affected

MTAP (HGNC:7413): (methylthioadenosine phosphorylase) This gene encodes an enzyme that plays a major role in polyamine metabolism and is important for the salvage pathway of both adenine and methionine. The encoded enzyme is deficient in many cancers. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Sep 2021]

MTAP Gene-Disease associations (from GenCC):

• diaphyseal medullary stenosis-bone malignancy syndrome

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Genomics England PanelApp, G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000264545 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 9-21864099-G-A is Benign according to our data. Variant chr9-21864099-G-A is described in ClinVar as Benign. ClinVar VariationId is 366288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002451.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTAP	NM_002451.4	MANE Select	c.*2085G>A		3_prime_UTR	Exon 8 of 8	NP_002442.2
	MTAP	NR_173242.1		n.3067G>A		non_coding_transcript_exon	Exon 8 of 8
	MTAP	NM_001396040.1		c.*2085G>A		3_prime_UTR	Exon 8 of 8	NP_001382969.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTAP	ENST00000644715.2	MANE Select	c.*2085G>A		3_prime_UTR	Exon 8 of 8	ENSP00000494373.1
	MTAP	ENST00000580900.5	TSL:1	c.813+4674G>A		intron	N/A	ENSP00000463424.1
	MTAP	ENST00000577563.1	TSL:1	c.147+9229G>A		intron	N/A	ENSP00000462082.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36980 AN: 151974 Hom.: 4816 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.255

GnomAD4 exome AF: 0.200 AC: 166336 AN: 833056 Hom.: 16972 Cov.: 35 AF XY: 0.199 AC XY: 76675 AN XY: 384690

African (AFR) AF: 0.253 AC: 3994 AN: 15786

American (AMR) AF: 0.422 AC: 415 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 1106 AN: 5150

East Asian (EAS) AF: 0.389 AC: 1412 AN: 3630

South Asian (SAS) AF: 0.244 AC: 4013 AN: 16460

European-Finnish (FIN) AF: 0.218 AC: 62 AN: 284

Middle Eastern (MID) AF: 0.235 AC: 380 AN: 1620

European-Non Finnish (NFE) AF: 0.196 AC: 149024 AN: 761844

Other (OTH) AF: 0.217 AC: 5930 AN: 27298

GnomAD4 genome AF: 0.244 AC: 37061 AN: 152092 Hom.: 4844 Cov.: 32 AF XY: 0.248 AC XY: 18399 AN XY: 74328

African (AFR) AF: 0.248 AC: 10296 AN: 41502

American (AMR) AF: 0.369 AC: 5642 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 754 AN: 3466

East Asian (EAS) AF: 0.383 AC: 1979 AN: 5164

South Asian (SAS) AF: 0.239 AC: 1152 AN: 4820

European-Finnish (FIN) AF: 0.216 AC: 2276 AN: 10552

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14022 AN: 67988

Other (OTH) AF: 0.260 AC: 549 AN: 2114

Alfa AF: 0.220 Hom.: 4932

Bravo AF: 0.258

Asia WGS AF: 0.317 AC: 1102 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Diaphyseal medullary stenosis-bone malignancy syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.39
DANN	Benign	0.30
PhyloP100		-0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs10117507; hg19: chr9-21864098; COSMIC: COSV66478392; COSMIC: COSV66478392;