rs1887465

Variant names:

• chr10-29458488-C-G
• rs1887465
• NM_021738.3:c.6504G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-29458488-C-G
• chr10-29458488-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021738.3(SVIL):​c.6504G>C​(p.Pro2168Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P2168P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SVIL NM_021738.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76
• Publications: 18 publications found

Genes affected

SVIL (HGNC:11480): (supervillin) This gene encodes a bipartite protein with distinct amino- and carboxy-terminal domains. The amino-terminus contains nuclear localization signals and the carboxy-terminus contains numerous consecutive sequences with extensive similarity to proteins in the gelsolin family of actin-binding proteins, which cap, nucleate, and/or sever actin filaments. The gene product is tightly associated with both actin filaments and plasma membranes, suggesting a role as a high-affinity link between the actin cytoskeleton and the membrane. The encoded protein appears to aid in both myosin II assembly during cell spreading and disassembly of focal adhesions. Several transcript variants encoding different isoforms of supervillin have been described. [provided by RefSeq, Apr 2016]

SVIL-AS1 (HGNC:):

SVIL-AS1 (HGNC:51219): (SVIL antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021738.3. 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
	SVIL	NM_021738.3	MANE Select	c.6504G>C	p.Pro2168Pro	synonymous	Exon 37 of 38	NP_068506.2	O95425-1
	SVIL	NM_001323599.2		c.5574G>C	p.Pro1858Pro	synonymous	Exon 38 of 39	NP_001310528.1	A0A6I8PIX7
	SVIL	NM_001323600.1		c.5322G>C	p.Pro1774Pro	synonymous	Exon 36 of 37	NP_001310529.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SVIL	ENST00000355867.9	TSL:1 MANE Select	c.6504G>C	p.Pro2168Pro	synonymous	Exon 37 of 38	ENSP00000348128.4	O95425-1
	SVIL	ENST00000375400.7	TSL:1	c.5226G>C	p.Pro1742Pro	synonymous	Exon 35 of 36	ENSP00000364549.3	O95425-2
	SVIL-AS1	ENST00000413405.7	TSL:1	n.212-28667C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.11
DANN	Benign	0.80
PhyloP100		-1.8

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: rs1887465; hg19: chr10-29747417; COSMIC: COSV63443886; COSMIC: COSV63443886;