17-41084428-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_033061.4(KRTAP4-7):​c.222C>T​(p.Cys74=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00483 in 1,419,176 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 0 hom., cov: 28)
Exomes 𝑓: 0.0051 ( 24 hom. )

Consequence

KRTAP4-7
NM_033061.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.31
Variant links:
Genes affected
KRTAP4-7 (HGNC:18898): (keratin associated protein 4-7) This protein is a member of the keratin-associated protein (KAP) family. The KAP proteins form a matrix of keratin intermediate filaments which contribute to the structure of hair fibers. KAP family members appear to have unique, family-specific amino- and carboxyl-terminal regions and are subdivided into three multi-gene families according to amino acid composition: the high sulfur, the ultrahigh sulfur, and the high tyrosine/glycine KAPs. This protein is a member of the ultrahigh sulfur KAP family and the gene is localized to a cluster of KAPs at 17q12-q21. [provided by RefSeq, Mar 2009]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant 17-41084428-C-T is Benign according to our data. Variant chr17-41084428-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3341590.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.31 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 24 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KRTAP4-7NM_033061.4 linkuse as main transcriptc.222C>T p.Cys74= synonymous_variant 1/1 ENST00000391417.6 NP_149050.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KRTAP4-7ENST00000391417.6 linkuse as main transcriptc.222C>T p.Cys74= synonymous_variant 1/1 NM_033061.4 ENSP00000375236 P1

Frequencies

GnomAD3 genomes
AF:
0.00254
AC:
383
AN:
150832
Hom.:
0
Cov.:
28
show subpopulations
Gnomad AFR
AF:
0.000767
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00309
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000416
Gnomad FIN
AF:
0.000283
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00438
Gnomad OTH
AF:
0.00145
GnomAD3 exomes
AF:
0.00269
AC:
671
AN:
249238
Hom.:
1
AF XY:
0.00264
AC XY:
357
AN XY:
135474
show subpopulations
Gnomad AFR exome
AF:
0.000329
Gnomad AMR exome
AF:
0.00336
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00111
Gnomad FIN exome
AF:
0.000416
Gnomad NFE exome
AF:
0.00422
Gnomad OTH exome
AF:
0.00477
GnomAD4 exome
AF:
0.00510
AC:
6469
AN:
1268234
Hom.:
24
Cov.:
141
AF XY:
0.00501
AC XY:
3160
AN XY:
630338
show subpopulations
Gnomad4 AFR exome
AF:
0.000927
Gnomad4 AMR exome
AF:
0.00420
Gnomad4 ASJ exome
AF:
0.0000499
Gnomad4 EAS exome
AF:
0.0000937
Gnomad4 SAS exome
AF:
0.00125
Gnomad4 FIN exome
AF:
0.000503
Gnomad4 NFE exome
AF:
0.00609
Gnomad4 OTH exome
AF:
0.00428
GnomAD4 genome
AF:
0.00254
AC:
384
AN:
150942
Hom.:
0
Cov.:
28
AF XY:
0.00224
AC XY:
165
AN XY:
73816
show subpopulations
Gnomad4 AFR
AF:
0.000764
Gnomad4 AMR
AF:
0.00309
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000417
Gnomad4 FIN
AF:
0.000283
Gnomad4 NFE
AF:
0.00439
Gnomad4 OTH
AF:
0.00144
Alfa
AF:
0.00335
Hom.:
0
EpiCase
AF:
0.00339
EpiControl
AF:
0.00451

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenAug 01, 2024KRTAP4-7: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
CADD
Benign
12
DANN
Benign
0.72

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.20
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.20
Position offset: 12

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs556699029; hg19: chr17-39240680; API