NM_033448.3:c.1391T>G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• 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
• Publications: 25 publications found

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]

KRT71 Gene-Disease associations (from GenCC):

• isolated familial wooly hair disorder

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hypotrichosis 13

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033448.3. 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
	KRT71	NM_033448.3	MANE Select	c.1391T>G	p.Val464Gly	missense	Exon 9 of 9	NP_258259.1	Q3SY84

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT71	ENST00000267119.6	TSL:1 MANE Select	c.1391T>G	p.Val464Gly	missense	Exon 9 of 9	ENSP00000267119.5	Q3SY84

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

GnomAD2 exomes AF: 0.457 AC: 111394 AN: 243974 AF XY: 0.456

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 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

African (AFR) AF: 0.0788 AC: 2637 AN: 33466

American (AMR) AF: 0.516 AC: 22978 AN: 44554

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 15124 AN: 26120

East Asian (EAS) AF: 0.534 AC: 21192 AN: 39670

South Asian (SAS) AF: 0.308 AC: 26552 AN: 86210

European-Finnish (FIN) AF: 0.460 AC: 23760 AN: 51676

Middle Eastern (MID) AF: 0.547 AC: 3096 AN: 5662

European-Non Finnish (NFE) AF: 0.513 AC: 570174 AN: 1111032

Other (OTH) AF: 0.475 AC: 28587 AN: 60200

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

African (AFR) AF: 0.0932 AC: 3869 AN: 41498

American (AMR) AF: 0.471 AC: 7207 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2067 AN: 3470

East Asian (EAS) AF: 0.525 AC: 2709 AN: 5158

South Asian (SAS) AF: 0.299 AC: 1445 AN: 4826

European-Finnish (FIN) AF: 0.450 AC: 4767 AN: 10592

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34895 AN: 67944

Other (OTH) AF: 0.419 AC: 885 AN: 2114

Alfa AF: 0.478 Hom.: 65222

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		1.8
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
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10783518; hg19: chr12-52938497; COSMIC: COSV107252642;