NM_001388272.1:c.314G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001388272.1(SH2D4B):​c.314G>C​(p.Arg105Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,344 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R105Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

SH2D4B
NM_001388272.1 missense

Scores

5
8
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.85
Variant links:
Genes affected
SH2D4B (HGNC:31440): (SH2 domain containing 4B) Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SH2D4BNM_001388272.1 linkc.314G>C p.Arg105Pro missense_variant Exon 2 of 8 ENST00000646907.2 NP_001375201.1
SH2D4BNM_207372.2 linkc.314G>C p.Arg105Pro missense_variant Exon 2 of 7 NP_997255.2 Q5SQS7-2
SH2D4BNM_001145719.1 linkc.167G>C p.Arg56Pro missense_variant Exon 2 of 7 NP_001139191.1 Q5SQS7-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SH2D4BENST00000646907.2 linkc.314G>C p.Arg105Pro missense_variant Exon 2 of 8 NM_001388272.1 ENSP00000494732.1 A0A2R8Y5Q0
SH2D4BENST00000339284.6 linkc.314G>C p.Arg105Pro missense_variant Exon 2 of 7 2 ENSP00000345295.2 Q5SQS7-2
SH2D4BENST00000313455.5 linkc.167G>C p.Arg56Pro missense_variant Exon 2 of 7 2 ENSP00000314242.4 Q5SQS7-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461344
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726958
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.010
CADD
Pathogenic
32
DANN
Uncertain
1.0
Eigen
Pathogenic
0.79
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.92
D;D;D
M_CAP
Benign
0.021
T
MetaRNN
Uncertain
0.68
D;D;D
MetaSVM
Benign
-1.0
T
PrimateAI
Uncertain
0.55
T
PROVEAN
Pathogenic
-4.5
D;.;D
REVEL
Uncertain
0.40
Sift
Uncertain
0.0050
D;.;D
Sift4G
Uncertain
0.0060
D;.;D
Polyphen
1.0
D;.;D
Vest4
0.80
MutPred
0.31
Loss of MoRF binding (P = 0.0225);Loss of MoRF binding (P = 0.0225);.;
MVP
0.59
MPC
0.79
ClinPred
0.99
D
GERP RS
5.6
gMVP
0.87

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-82330039; API