chr2-9964030-C-G

Variant names:

• chr2-9964030-C-G
• NM_198182.3:c.891C>G

Variant summary

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

The NM_198182.3(GRHL1):​c.891C>G​(p.Ile297Met) 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. 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: 4.09
• 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 2 ACMG points.

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

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.891C>G	p.Ile297Met	missense	Exon 6 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.891C>G	p.Ile297Met	missense	Exon 6 of 16	ENSP00000324693.9	Q9NZI5-1
	GRHL1	ENST00000405379.6	TSL:1	c.324C>G	p.Ile108Met	missense	Exon 2 of 12	ENSP00000384209.3	Q9NZI5-2
	GRHL1	ENST00000472167.5	TSL:1	n.891C>G		non_coding_transcript_exon	Exon 6 of 16	ENSP00000418275.1	Q9NZI5-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	0.23
BayesDel_addAF	Benign	0.0039	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		4.1
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.18
Sift	Benign	0.037	D
Sift4G	Benign	0.10	T
Polyphen		1.0	D
Vest4		0.49
MutPred		0.41		Gain of catalytic residue at I297 (P = 0.0031)
MVP		0.22
MPC		1.1
ClinPred		0.92	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.53
gMVP		0.41
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.22		Position offset: -33

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr2-10104159;