12-52692529-T-G

Position:

• chr12-52692529-T-G

Variant summary

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

The NM_175078.3(KRT77):​c.1319A>C​(p.Glu440Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRT77 NM_175078.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.49

Genes affected

KRT77 (HGNC:20411): (keratin 77) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. This gene encodes an epithelial keratin that is expressed in the skin and eccrine sweat glands. The type II keratins are clustered in a region of chromosome 12q13.[provided by RefSeq, Jun 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
KRT77	NM_175078.3	c.1319A>C	p.Glu440Ala	missense_variant	7/9	ENST00000341809.8	NP_778253.2
KRT77	XM_011538288.3	c.620A>C	p.Glu207Ala	missense_variant	7/9		XP_011536590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT77	ENST00000341809.8	c.1319A>C	p.Glu440Ala	missense_variant	7/9	1	NM_175078.3	ENSP00000342710.3
KRT77	ENST00000553168.1	n.*657A>C		non_coding_transcript_exon_variant	8/10	1		ENSP00000448207.1
KRT77	ENST00000553168.1	n.*657A>C		3_prime_UTR_variant	8/10	1		ENSP00000448207.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2021

The c.1319A>C (p.E440A) alteration is located in exon 7 (coding exon 7) of the KRT77 gene. This alteration results from a A to C substitution at nucleotide position 1319, causing the glutamic acid (E) at amino acid position 440 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.068	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Uncertain	0.58	D
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.42
Sift	Benign	0.050	D
Sift4G	Benign	0.18	T
Polyphen		0.99	D
Vest4		0.43
MutPred		0.50		Gain of MoRF binding (P = 0.0627);
MVP		0.95
MPC		0.68
ClinPred		0.99	D
GERP RS		4.3
Varity_R		0.42
gMVP		0.32

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: chr12-53086313;