12-52544713-A-C

Variant names:

• chr12-52544713-A-C
• rs10783518
• NM_033448.3:c.1391T>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_033448.3(KRT71):​c.1391T>G​(p.Val464Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 1,610,686 control chromosomes in the GnomAD database, including 194,453 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.38 (13953 hom., cov: 33)
  • Exomes 𝑓: 0.49 (180500 hom.)
• Consequence: KRT71 NM_033448.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.76

Genes affected

KRT71 (HGNC:28927): (keratin 71) 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 a protein that is expressed in the inner root sheath of hair follicles. The type II keratins are clustered in a region of chromosome 12q13.[provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.0458344E-5).
• BP6: Variant 12-52544713-A-C is Benign according to our data. Variant chr12-52544713-A-C is described in ClinVar as [Benign]. Clinvar id is 1283050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT71	NM_033448.3	c.1391T>G	p.Val464Gly	missense_variant	Exon 9 of 9	ENST00000267119.6	NP_258259.1
KRT71	XM_047428197.1	c.1265T>G	p.Val422Gly	missense_variant	Exon 8 of 8		XP_047284153.1
KRT71	XM_017018749.2	c.1145T>G	p.Val382Gly	missense_variant	Exon 10 of 10		XP_016874238.1
KRT71	XM_047428196.1	c.1030-364T>G		intron_variant	Intron 6 of 6		XP_047284152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT71	ENST00000267119.6	c.1391T>G	p.Val464Gly	missense_variant	Exon 9 of 9	1	NM_033448.3	ENSP00000267119.5

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58503 AN: 151978 Hom.: 13960 Cov.: 33

Gnomad AFR AF: 0.0935

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.423

GnomAD3 exomes AF: 0.457 AC: 111394 AN: 243974 Hom.: 27454 AF XY: 0.456 AC XY: 60513 AN XY: 132820

Gnomad AFR exome AF: 0.0826

Gnomad AMR exome AF: 0.526

Gnomad ASJ exome AF: 0.575

Gnomad EAS exome AF: 0.511

Gnomad SAS exome AF: 0.305

Gnomad FIN exome AF: 0.454

Gnomad NFE exome AF: 0.508

Gnomad OTH exome AF: 0.497

GnomAD4 exome AF: 0.490 AC: 714100 AN: 1458590 Hom.: 180500 Cov.: 53 AF XY: 0.485 AC XY: 352250 AN XY: 725646

Gnomad4 AFR exome AF: 0.0788

Gnomad4 AMR exome AF: 0.516

Gnomad4 ASJ exome AF: 0.579

Gnomad4 EAS exome AF: 0.534

Gnomad4 SAS exome AF: 0.308

Gnomad4 FIN exome AF: 0.460

Gnomad4 NFE exome AF: 0.513

Gnomad4 OTH exome AF: 0.475

GnomAD4 genome AF: 0.385 AC: 58483 AN: 152096 Hom.: 13953 Cov.: 33 AF XY: 0.384 AC XY: 28523 AN XY: 74356

Gnomad4 AFR AF: 0.0932

Gnomad4 AMR AF: 0.471

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.419

Alfa AF: 0.498 Hom.: 46486

Bravo AF: 0.378

TwinsUK AF: 0.498 AC: 1847

ALSPAC AF: 0.499 AC: 1923

ESP6500AA AF: 0.0952 AC: 414

ESP6500EA AF: 0.481 AC: 4099

ExAC AF: 0.429 AC: 51366

Asia WGS AF: 0.358 AC: 1243 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	13
DANN	Benign	0.84
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.0043	N
LIST_S2	Benign	0.0087	T
MetaRNN	Benign	0.000050	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.9	N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	5.1	N
REVEL	Benign	0.10
Sift	Benign	0.64	T
Sift4G	Benign	0.52	T
Polyphen		0.0	B
Vest4		0.048
MPC		0.12
ClinPred		0.0050	T
GERP RS		2.6
Varity_R		0.066
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs10783518; hg19: chr12-52938497;