rs766540105

Variant names:

• chr2-9958846-C-A
• rs766540105
• NM_198182.3:c.268C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-9958846-C-A
• chr2-9958846-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198182.3(GRHL1):​c.268C>A​(p.His90Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GRHL1 NM_198182.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.72
• Publications: 0 publications found

Genes affected

GRHL1 (HGNC:17923): (grainyhead like transcription factor 1) This gene encodes a member of the grainyhead family of transcription factors. The encoded protein can exist as a homodimer or can form heterodimers with sister-of-mammalian grainyhead or brother-of-mammalian grainyhead. This protein functions as a transcription factor during development. [provided by RefSeq, Jun 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.123217344).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198182.3. 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
	GRHL1	NM_198182.3	MANE Select	c.268C>A	p.His90Asn	missense	Exon 3 of 16	NP_937825.2	Q9NZI5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRHL1	ENST00000324907.14	TSL:1 MANE Select	c.268C>A	p.His90Asn	missense	Exon 3 of 16	ENSP00000324693.9	Q9NZI5-1
	GRHL1	ENST00000472167.5	TSL:1	n.268C>A		non_coding_transcript_exon	Exon 3 of 16	ENSP00000418275.1	Q9NZI5-3
	GRHL1	ENST00000439493.5	TSL:5	n.268C>A		non_coding_transcript_exon	Exon 3 of 4	ENSP00000387521.1	F8WFB0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		5.7
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.059
Sift	Benign	0.044	D
Sift4G	Benign	0.20	T
Polyphen		0.14	B
Vest4		0.37
MutPred		0.19		Loss of glycosylation at S95 (P = 0.1752)
MVP		0.12
MPC		0.49
ClinPred		0.76	D
GERP RS		5.2
Varity_R		0.17
gMVP		0.19
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs766540105; hg19: chr2-10098975;