chr19-39370044-C-G

Variant names:

• chr19-39370044-C-G
• rs763237352
• NM_001384574.2:c.586C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001384574.2(SAMD4B):​c.586C>G​(p.Arg196Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 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. R196W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SAMD4B NM_001384574.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.625
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06448245).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384574.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMD4B	NM_001384574.2	MANE Select	c.586C>G	p.Arg196Gly	missense	Exon 4 of 14	NP_001371503.1	Q5PRF9
	SAMD4B	NM_001384565.1		c.586C>G	p.Arg196Gly	missense	Exon 4 of 14	NP_001371494.1	Q5PRF9
	SAMD4B	NM_001384566.1		c.586C>G	p.Arg196Gly	missense	Exon 5 of 15	NP_001371495.1	Q5PRF9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMD4B	ENST00000610417.5	TSL:2 MANE Select	c.586C>G	p.Arg196Gly	missense	Exon 4 of 14	ENSP00000484229.1	Q5PRF9
	SAMD4B	ENST00000314471.10	TSL:1	c.586C>G	p.Arg196Gly	missense	Exon 6 of 16	ENSP00000317224.5	Q5PRF9
	SAMD4B	ENST00000598913.5	TSL:1	c.586C>G	p.Arg196Gly	missense	Exon 3 of 13	ENSP00000470237.1	M0QZ22

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000410 AC: 1 AN: 243690 AF XY: 0.00000755

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000910

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459636 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726004

African (AFR) AF: 0.00 AC: 0 AN: 33390

American (AMR) AF: 0.00 AC: 0 AN: 44456

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39538

South Asian (SAS) AF: 0.00 AC: 0 AN: 85888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53160

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111066

Other (OTH) AF: 0.00 AC: 0 AN: 60268

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Benign	0.90
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.62	N
PhyloP100		0.63
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.29	N
REVEL	Benign	0.13
Sift	Benign	0.21	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.26
MutPred		0.25		Loss of solvent accessibility (P = 0.0013)
MVP		0.043
MPC		0.90
ClinPred		0.042	T
GERP RS		1.7
PromoterAI		-0.016	Neutral
Varity_R		0.080
gMVP		0.53
Mutation Taster		=63/37	polymorphism

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

Other links and lift over

dbSNP: rs763237352; hg19: chr19-39860684;