chr4-39552152-C-A

Variant names:

• chr4-39552152-C-A
• rs1181290687
• NM_174921.3:c.274G>T

Variant summary

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

The NM_174921.3(SMIM14):​c.274G>T​(p.Asp92Tyr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMIM14 NM_174921.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.77
• Publications: 0 publications found

Genes affected

SMIM14 (HGNC:27321): (small integral membrane protein 14) Predicted to act upstream of or within blastocyst hatching. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

UGDH-AS1 (HGNC:40601): (UGDH antisense RNA 1)

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=0.20930043).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174921.3. 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
	SMIM14	NM_174921.3	MANE Select	c.274G>T	p.Asp92Tyr	missense	Exon 5 of 5	NP_777581.1	Q96QK8
	SMIM14	NM_001317896.2		c.274G>T	p.Asp92Tyr	missense	Exon 6 of 6	NP_001304825.1	Q96QK8
	SMIM14	NM_001317897.2		c.274G>T	p.Asp92Tyr	missense	Exon 5 of 5	NP_001304826.1	Q96QK8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMIM14	ENST00000295958.10	TSL:1 MANE Select	c.274G>T	p.Asp92Tyr	missense	Exon 5 of 5	ENSP00000295958.4	Q96QK8
	SMIM14	ENST00000865444.1		c.274G>T	p.Asp92Tyr	missense	Exon 5 of 5	ENSP00000535503.1
	SMIM14	ENST00000865445.1		c.274G>T	p.Asp92Tyr	missense	Exon 6 of 6	ENSP00000535504.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

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	0.19
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.44	T
PhyloP100		4.8
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.12
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.028	D
Polyphen		0.79	P
Vest4		0.26
MutPred		0.23		Gain of phosphorylation at D92 (P = 0.0051)
MVP		0.21
MPC		1.5
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.31
gMVP		0.45
Mutation Taster		=63/37	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1181290687; hg19: chr4-39553772;