chr10-7172098-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001387889.1(SFMBT2):ā€‹c.2212T>Cā€‹(p.Ser738Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,452,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

SFMBT2
NM_001387889.1 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.44
Variant links:
Genes affected
SFMBT2 (HGNC:20256): (Scm like with four mbt domains 2) Enables histone binding activity. Involved in negative regulation of gene expression. Located in aggresome; cytosol; and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18813798).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SFMBT2NM_001387889.1 linkuse as main transcriptc.2212T>C p.Ser738Pro missense_variant 19/21 ENST00000397167.6 NP_001374818.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SFMBT2ENST00000397167.6 linkuse as main transcriptc.2212T>C p.Ser738Pro missense_variant 19/215 NM_001387889.1 ENSP00000380353 P4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.88e-7
AC:
1
AN:
1452734
Hom.:
0
Cov.:
32
AF XY:
0.00000139
AC XY:
1
AN XY:
721772
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:
0.00
Gnomad4 NFE exome
AF:
9.03e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 12, 2022The c.2212T>C (p.S738P) alteration is located in exon 19 (coding exon 18) of the SFMBT2 gene. This alteration results from a T to C substitution at nucleotide position 2212, causing the serine (S) at amino acid position 738 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.064
T;T
Eigen
Benign
0.023
Eigen_PC
Benign
0.14
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.87
.;D
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.19
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.8
M;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.62
T
PROVEAN
Uncertain
-2.6
D;D
REVEL
Benign
0.11
Sift
Benign
0.041
D;D
Sift4G
Uncertain
0.049
D;D
Polyphen
0.0060
B;B
Vest4
0.36
MutPred
0.24
Loss of phosphorylation at S738 (P = 0.0017);Loss of phosphorylation at S738 (P = 0.0017);
MVP
0.11
MPC
0.17
ClinPred
0.97
D
GERP RS
5.3
Varity_R
0.59
gMVP
0.33

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: chr10-7214060; COSMIC: COSV62813898; API