rs878853009

Variant names:

• chr4-78534471-C-A
• NM_025074.7:c.10948C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-78534471-C-A
• chr4-78534471-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_025074.7(FRAS1):​c.10948C>A​(p.Gln3650Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FRAS1 NM_025074.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.75

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.846

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRAS1	NM_025074.7	c.10948C>A	p.Gln3650Lys	missense_variant	Exon 71 of 74	ENST00000512123.4	NP_079350.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRAS1	ENST00000512123.4	c.10948C>A	p.Gln3650Lys	missense_variant	Exon 71 of 74	5	NM_025074.7	ENSP00000422834.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	26
DANN	Uncertain	0.99
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	-0.16	T
PrimateAI	Pathogenic	0.80	D
Sift4G	Pathogenic	0.0	D
Vest4		0.84
MVP		0.81
ClinPred		0.98	D
GERP RS		4.5
gMVP		0.83

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-79455625;