NM_001384574.2:c.485C>T

Variant names:

• chr19-39369943-C-T
• rs2077186898
• NM_001384574.2:c.485C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001384574.2(SAMD4B):​c.485C>T​(p.Pro162Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P162R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SAMD4B NM_001384574.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.79
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14705369).

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.485C>T	p.Pro162Leu	missense	Exon 4 of 14	NP_001371503.1	Q5PRF9
	SAMD4B	NM_001384565.1		c.485C>T	p.Pro162Leu	missense	Exon 4 of 14	NP_001371494.1	Q5PRF9
	SAMD4B	NM_001384566.1		c.485C>T	p.Pro162Leu	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.485C>T	p.Pro162Leu	missense	Exon 4 of 14	ENSP00000484229.1	Q5PRF9
	SAMD4B	ENST00000314471.10	TSL:1	c.485C>T	p.Pro162Leu	missense	Exon 6 of 16	ENSP00000317224.5	Q5PRF9
	SAMD4B	ENST00000598913.5	TSL:1	c.485C>T	p.Pro162Leu	missense	Exon 3 of 13	ENSP00000470237.1	M0QZ22

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.056	T
Eigen	Benign	-0.054
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.8
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.091
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.26	T
Polyphen		0.020	B
Vest4		0.21
MutPred		0.16		Loss of glycosylation at P162 (P = 0.034)
MVP		0.068
MPC		0.71
ClinPred		0.82	D
GERP RS		5.2
PromoterAI		0.0014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.081
gMVP		0.56
Mutation Taster		=79/21	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: rs2077186898; hg19: chr19-39860583;