rs754006408

Variant names:

• chr1-24331548-T-A
• rs754006408
• ENST00000356046.6:c.2T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-24331548-T-A
• chr1-24331548-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PVS1_Supporting PM2

The NM_001195010.2(GRHL3):​c.2T>A​(p.Met1?) variant causes a start lost change. 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: GRHL3 NM_001195010.2 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.17

Genes affected

GRHL3 (HGNC:25839): (grainyhead like transcription factor 3) This gene encodes a member of the grainyhead family of transcription factors. The encoded protein may function as a transcription factor during development, and has been shown to stimulate migration of endothelial cells. Multiple transcript variants encoding distinct isoforms have been identified for this gene.[provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 2 codons. Genomic position: 24331550. Lost 0.002 part of the original CDS.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRHL3	NM_198173.3	c.140T>A	p.Met47Lys	missense_variant	Exon 2 of 16	ENST00000361548.9	NP_937816.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRHL3	ENST00000361548.9	c.140T>A	p.Met47Lys	missense_variant	Exon 2 of 16	1	NM_198173.3	ENSP00000354943.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.63	.;D;.;.;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D;D;D;D;D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.72	D;D;D;D;D
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.6	M;M;.;.;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.8	D;D;D;D;D
REVEL	Uncertain	0.43
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Uncertain	0.042	D;D;D;D;D
Polyphen		0.44	.;.;.;.;B
Vest4		0.83
MutPred		0.53		Gain of ubiquitination at M47 (P = 0.0185);Gain of ubiquitination at M47 (P = 0.0185);.;.;.;
MVP		0.40
MPC		1.0
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.89
gMVP		0.76

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: rs754006408; hg19: chr1-24658038;