4-78066003-A-T

Position:

• chr4-78066003-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025074.7(FRAS1):​c.95A>T​(p.Asp32Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D32G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FRAS1 NM_025074.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.81

Genes affected

FRAS1 (HGNC:19185): (Fraser extracellular matrix complex subunit 1) This gene encodes an extracellular matrix protein that appears to function in the regulation of epidermal-basement membrane adhesion and organogenesis during development. Mutations in this gene cause Fraser syndrome, a multisystem malformation that can include craniofacial, urogenital and respiratory system abnormalities. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRAS1	NM_025074.7	c.95A>T	p.Asp32Val	missense_variant	2/74	ENST00000512123.4	NP_079350.5
FRAS1	NM_001166133.2	c.95A>T	p.Asp32Val	missense_variant	2/42		NP_001159605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRAS1	ENST00000512123.4	c.95A>T	p.Asp32Val	missense_variant	2/74	5	NM_025074.7	ENSP00000422834	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1452580 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 722982

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	0.98
Eigen	Benign	-0.017
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.54	T;T
M_CAP	Uncertain	0.090	D
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	0.81	L;L
MutationTaster	Benign	0.053	P;P;P
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.17	N;D
REVEL	Benign	0.27
Sift	Uncertain	0.0070	D;D
Sift4G	Benign	0.19	T;T
Vest4		0.43
MutPred		0.57		Loss of glycosylation at S33 (P = 0.0383);Loss of glycosylation at S33 (P = 0.0383);
MVP		0.74
ClinPred		0.73	D
GERP RS		5.9
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs4859905; hg19: chr4-78987157;