chr12-52241479-C-A

Variant names:

• chr12-52241479-C-A
• rs139062982
• NM_005556.4:c.701C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005556.4(KRT7):​c.701C>A​(p.Thr234Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T234R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: KRT7 NM_005556.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050744623).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005556.4. 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
	KRT7	NM_005556.4	MANE Select	c.701C>A	p.Thr234Lys	missense	Exon 5 of 9	NP_005547.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT7	ENST00000331817.6	TSL:1 MANE Select	c.701C>A	p.Thr234Lys	missense	Exon 5 of 9	ENSP00000329243.5	P08729
	KRT7	ENST00000955643.1		c.773C>A	p.Thr258Lys	missense	Exon 6 of 10	ENSP00000625702.1
	KRT7	ENST00000955640.1		c.770C>A	p.Thr257Lys	missense	Exon 6 of 10	ENSP00000625699.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458468 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725456

African (AFR) AF: 0.00 AC: 0 AN: 33352

American (AMR) AF: 0.00 AC: 0 AN: 44460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25870

East Asian (EAS) AF: 0.00 AC: 0 AN: 39552

South Asian (SAS) AF: 0.00 AC: 0 AN: 85726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110170

Other (OTH) AF: 0.00 AC: 0 AN: 60252

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.13	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.49	N
PhyloP100		-0.085
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.15
Sift	Benign	0.083	T
Sift4G	Benign	0.45	T
Polyphen		0.0020	B
Vest4		0.12
MutPred		0.38		Gain of ubiquitination at T234 (P = 0.0211)
MVP		0.30
MPC		0.34
ClinPred		0.079	T
GERP RS		0.76
Varity_R		0.049
gMVP		0.31
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs139062982; hg19: chr12-52635263;