7-99052428-G-T

Position:

• chr7-99052428-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_181349.3(SMURF1):​c.498C>A​(p.Ser166=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000495 in 1,580,132 control chromosomes in the GnomAD database, including 5 homozygotes. 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. S166S) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0025 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00029 (4 hom.)
• Consequence: SMURF1 NM_181349.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.18

Genes affected

SMURF1 (HGNC:16807): (SMAD specific E3 ubiquitin protein ligase 1) This gene encodes a ubiquitin ligase that is specific for receptor-regulated SMAD proteins in the bone morphogenetic protein (BMP) pathway. This protein plays a key roll in the regulation of cell motility, cell signalling, and cell polarity. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-6.18 with no splicing effect.
• BS2: High AC in GnomAd4 at 375 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMURF1	NM_181349.3	c.498C>A	p.Ser166=	synonymous_variant	7/18	ENST00000361368.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMURF1	ENST00000361368.7	c.498C>A	p.Ser166=	synonymous_variant	7/18	1	NM_181349.3	P1
SMURF1	ENST00000361125.1	c.498C>A	p.Ser166=	synonymous_variant	7/19	1
SMURF1	ENST00000480055.5	n.796C>A		non_coding_transcript_exon_variant	7/7	3

Frequencies

GnomAD3 genomes AF: 0.00247 AC: 376 AN: 152034 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00864

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000773 AC: 177 AN: 228896 Hom.: 2 AF XY: 0.000479 AC XY: 59 AN XY: 123176

Gnomad AFR exome AF: 0.00948

Gnomad AMR exome AF: 0.000565

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000563

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000380

Gnomad OTH exome AF: 0.000733

GnomAD4 exome AF: 0.000285 AC: 407 AN: 1427980 Hom.: 4 Cov.: 49 AF XY: 0.000226 AC XY: 160 AN XY: 706672

Gnomad4 AFR exome AF: 0.00784

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000622

Gnomad4 OTH exome AF: 0.000577

GnomAD4 genome AF: 0.00246 AC: 375 AN: 152152 Hom.: 1 Cov.: 33 AF XY: 0.00219 AC XY: 163 AN XY: 74374

Gnomad4 AFR AF: 0.00859

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.0000517 Hom.: 2411

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs219797; hg19: chr7-98650051;