NM_001077621.2:c.279C>T

Variant names:

• chr7-73669559-C-T
• rs61743139
• NM_001077621.2:c.279C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001077621.2(VPS37D):​c.279C>T​(p.Ala93Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,592,400 control chromosomes in the GnomAD database, including 102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0069 (4 hom., cov: 32)
  • Exomes 𝑓: 0.011 (98 hom.)
• Consequence: VPS37D NM_001077621.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.87
• Publications: 3 publications found

Genes affected

VPS37D (HGNC:18287): (VPS37D subunit of ESCRT-I) Predicted to be involved in protein targeting to membrane; protein targeting to vacuole; and ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway. Located in extracellular exosome. Part of ESCRT I complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 7-73669559-C-T is Benign according to our data. Variant chr7-73669559-C-T is described in ClinVar as Benign. ClinVar VariationId is 2579019.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.87 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077621.2. 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
	VPS37D	NM_001077621.2	MANE Select	c.279C>T	p.Ala93Ala	synonymous	Exon 2 of 4	NP_001071089.1	Q86XT2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS37D	ENST00000324941.5	TSL:1 MANE Select	c.279C>T	p.Ala93Ala	synonymous	Exon 2 of 4	ENSP00000320416.4	Q86XT2
	VPS37D	ENST00000965880.1		c.279C>T	p.Ala93Ala	synonymous	Exon 2 of 4	ENSP00000635939.1
	VPS37D	ENST00000903466.1		c.279C>T	p.Ala93Ala	synonymous	Exon 2 of 4	ENSP00000573525.1

Frequencies

GnomAD3 genomes AF: 0.00695 AC: 1058 AN: 152180 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00210

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00307

Gnomad ASJ AF: 0.0132

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.00612

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0115

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00706 AC: 1472 AN: 208556 AF XY: 0.00702

Gnomad AFR exome AF: 0.00205

Gnomad AMR exome AF: 0.00505

Gnomad ASJ exome AF: 0.00830

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00562

Gnomad NFE exome AF: 0.0110

Gnomad OTH exome AF: 0.00608

GnomAD4 exome AF: 0.0105 AC: 15180 AN: 1440102 Hom.: 98 Cov.: 31 AF XY: 0.0103 AC XY: 7368 AN XY: 714088

African (AFR) AF: 0.00151 AC: 50 AN: 33076

American (AMR) AF: 0.00476 AC: 198 AN: 41578

Ashkenazi Jewish (ASJ) AF: 0.00873 AC: 224 AN: 25656

East Asian (EAS) AF: 0.00 AC: 0 AN: 38684

South Asian (SAS) AF: 0.00327 AC: 270 AN: 82648

European-Finnish (FIN) AF: 0.00523 AC: 270 AN: 51640

Middle Eastern (MID) AF: 0.00227 AC: 13 AN: 5724

European-Non Finnish (NFE) AF: 0.0124 AC: 13611 AN: 1101590

Other (OTH) AF: 0.00914 AC: 544 AN: 59506

GnomAD4 genome AF: 0.00695 AC: 1058 AN: 152298 Hom.: 4 Cov.: 32 AF XY: 0.00679 AC XY: 506 AN XY: 74478

African (AFR) AF: 0.00209 AC: 87 AN: 41568

American (AMR) AF: 0.00307 AC: 47 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0132 AC: 46 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4824

European-Finnish (FIN) AF: 0.00612 AC: 65 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0115 AC: 784 AN: 68010

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.00991 Hom.: 4

Bravo AF: 0.00686

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	0.26
DANN	Benign	0.78
PhyloP100		-4.9
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: rs61743139; hg19: chr7-73083889; COSMIC: COSV61446444;