17-35548498-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001129820.2(SLFN14):​c.2480G>A​(p.Arg827His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,551,730 control chromosomes in the GnomAD database, including 2 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00018 ( 2 hom. )

Consequence

SLFN14
NM_001129820.2 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.568
Variant links:
Genes affected
SLFN14 (HGNC:32689): (schlafen family member 14) The protein encoded by this gene plays an important role in platelet formation and function. Defects in this gene are a cause of thrombocytopenia with excessive bleeding. [provided by RefSeq, Jul 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.007407367).
BP6
Variant 17-35548498-C-T is Benign according to our data. Variant chr17-35548498-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3892506.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLFN14NM_001129820.2 linkc.2480G>A p.Arg827His missense_variant Exon 6 of 6 ENST00000674182.1 NP_001123292.1 P0C7P3-1
SLFN14XM_017024577.2 linkc.2480G>A p.Arg827His missense_variant Exon 6 of 6 XP_016880066.1 P0C7P3-1
SLFN14XM_017024578.2 linkc.2480G>A p.Arg827His missense_variant Exon 5 of 5 XP_016880067.1 P0C7P3-1
SLFN14XM_017024579.2 linkc.2480G>A p.Arg827His missense_variant Exon 5 of 5 XP_016880068.1 P0C7P3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLFN14ENST00000674182.1 linkc.2480G>A p.Arg827His missense_variant Exon 6 of 6 NM_001129820.2 ENSP00000501524.1 P0C7P3-1
SLFN14ENST00000415846.3 linkc.2480G>A p.Arg827His missense_variant Exon 4 of 4 1 ENSP00000391101.2 P0C7P3-1

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152222
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00115
Gnomad SAS
AF:
0.00166
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000526
AC:
81
AN:
153952
Hom.:
1
AF XY:
0.000686
AC XY:
56
AN XY:
81688
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000550
Gnomad SAS exome
AF:
0.00329
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000184
AC:
257
AN:
1399390
Hom.:
2
Cov.:
33
AF XY:
0.000255
AC XY:
176
AN XY:
690206
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000224
Gnomad4 SAS exome
AF:
0.00290
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000371
Gnomad4 OTH exome
AF:
0.000224
GnomAD4 genome
AF:
0.0000985
AC:
15
AN:
152340
Hom.:
0
Cov.:
33
AF XY:
0.000148
AC XY:
11
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00135
Gnomad4 SAS
AF:
0.00166
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000138
Hom.:
0
Bravo
AF:
0.0000416
ExAC
AF:
0.00105
AC:
25
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

ClinVar

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

Submissions by phenotype

Platelet-type bleeding disorder 20 Benign:1
May 12, 2020
Department of Pathology and Laboratory Medicine, Sinai Health System
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.089
BayesDel_addAF
Benign
-0.63
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
15
DANN
Benign
0.77
DEOGEN2
Benign
0.00098
T
Eigen
Benign
-0.80
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.23
N
LIST_S2
Benign
0.71
T
M_CAP
Benign
0.0067
T
MetaRNN
Benign
0.0074
T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
1.4
L
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.015
Sift
Benign
0.38
T
Sift4G
Benign
0.50
T
Polyphen
0.0010
B
Vest4
0.11
MutPred
0.29
Loss of MoRF binding (P = 0.0214);
MVP
0.014
ClinPred
0.025
T
GERP RS
2.2
Varity_R
0.029
gMVP
0.27

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs562073297; hg19: chr17-33875517; API