dbSNP rs767556722: SAMD4B:p.Pro210Leu (chr19-39370087-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001384574.2(SAMD4B):c.629C>T(p.Pro210Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000213 in 1,453,642 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

SAMD4B
NM_001384574.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.38

Variant links:

Genes affected

SAMD4B (HGNC:25492): (sterile alpha motif domain containing 4B) Enables RNA binding activity. Predicted to be involved in nuclear-transcribed mRNA poly(A) tail shortening. Predicted to act upstream of or within cerebellar neuron development. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

SAMD4B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15555564).

BS2

High AC in GnomAdExome4 at 31 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMD4B	NM_001384574.2 link	c.629C>T	p.Pro210Leu	missense_variant	Exon 4 of 14	ENST00000610417.5	NP_001371503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAMD4B	ENST00000610417.5 link	c.629C>T	p.Pro210Leu	missense_variant	Exon 4 of 14	2	NM_001384574.2	ENSP00000484229.1		Q5PRF9
SAMD4B	ENST00000596368.1 link	c.629C>T	p.Pro210Leu	missense_variant	Exon 2 of 5	5		ENSP00000471509.1		M0R0X3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000215

AC:

AN:

232688

Hom.:

AF XY:

0.0000318

AC XY:

AN XY:

125946

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000303

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.0000497

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000213

AC:

AN:

1453642

Hom.:

Cov.:

AF XY:

0.0000194

AC XY:

AN XY:

722424

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000229

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000106

Gnomad4 FIN exome

AF:

0.0000379

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 11, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.629C>T (p.P210L) alteration is located in exon 6 (coding exon 2) of the SAMD4B gene. This alteration results from a C to T substitution at nucleotide position 629, causing the proline (P) at amino acid position 210 to be replaced by a leucine (L). 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

0.095

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;T;.;T;T;T

Eigen

Benign

-0.041

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;.;D;D;D;D

M_CAP

Benign

0.0079

MetaRNN

Benign

0.16

T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.0

.;M;.;M;.;.

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-6.4

.;D;.;.;.;.

REVEL

Benign

0.13

Sift

Uncertain

0.0010

.;D;.;.;.;.

Sift4G

Benign

0.22

T;T;D;T;T;D

Polyphen

0.0

.;B;.;B;.;.

Vest4

0.43

MutPred

0.28

Loss of glycosylation at S207 (P = 0.0506);Loss of glycosylation at S207 (P = 0.0506);Loss of glycosylation at S207 (P = 0.0506);Loss of glycosylation at S207 (P = 0.0506);Loss of glycosylation at S207 (P = 0.0506);Loss of glycosylation at S207 (P = 0.0506);

MVP

0.082

MPC

1.6

ClinPred

0.71

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.47

gMVP

0.62

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over