12-52243017-G-C

Variant summary

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

The NM_005556.4(KRT7):c.864G>C(p.Glu288Asp) 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: KRT7 NM_005556.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.73

Genes affected

KRT7 (HGNC:6445): (keratin 7) The protein encoded by this gene is a member of the keratin gene family. The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. This type II cytokeratin is specifically expressed in the simple epithelia lining the cavities of the internal organs and in the gland ducts and blood vessels. The genes encoding the type II cytokeratins are clustered in a region of chromosome 12q12-q13. Alternative splicing may result in several transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

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	UniProt
KRT7	NM_005556.4	c.864G>C	p.Glu288Asp	missense_variant	6/9	ENST00000331817.6
KRT7	XM_011538325.3	c.864G>C	p.Glu288Asp	missense_variant	6/8
KRT7	XM_047428827.1	c.864G>C	p.Glu288Asp	missense_variant	6/7
KRT7	XM_017019294.2	c.333G>C	p.Glu111Asp	missense_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT7	ENST00000331817.6	c.864G>C	p.Glu288Asp	missense_variant	6/9	1	NM_005556.4	P1
KRT7	ENST00000546856.5	n.228G>C		non_coding_transcript_exon_variant	3/4	3
KRT7	ENST00000551130.1	n.98G>C		non_coding_transcript_exon_variant	2/2	2
KRT7	ENST00000552183.1	n.115G>C		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Feb 28, 2024

The c.864G>C (p.E288D) alteration is located in exon 6 (coding exon 6) of the KRT7 gene. This alteration results from a G to C substitution at nucleotide position 864, causing the glutamic acid (E) at amino acid position 288 to be replaced by an aspartic acid (D). 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	0.27
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D;.
Eigen	Benign	0.11
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.8	D;.
REVEL	Uncertain	0.44
Sift	Uncertain	0.0090	D;.
Sift4G	Benign	0.081	T;.
Polyphen		0.44	B;.
Vest4		0.51
MutPred		0.45		Loss of ubiquitination at K286 (P = 0.1172);.;
MVP		0.82
MPC		0.78
ClinPred		0.95	D
GERP RS		3.9
Varity_R		0.39
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr12-52636801;