4-121761880-C-A

Variant names:

• chr4-121761880-C-A
• rs780379584
• NM_001384332.1:c.*291G>T

Variant summary

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

The NM_001384332.1(SMIM43):​c.*291G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,454,942 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: 0.0000034 (0 hom.)
• Consequence: SMIM43 NM_001384332.1 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.472
• Publications: 0 publications found

Genes affected

SMIM43 (HGNC:55077): (small integral membrane protein 43) Predicted to be integral component of membrane. [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=0.06356722).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384332.1. 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
	SMIM43	NM_001384332.1	MANE Select	c.*291G>T		3_prime_UTR	Exon 4 of 6	NP_001371261.1	Q4W5P6
	SMIM43	NM_001384333.1		c.*288G>T		3_prime_UTR	Exon 4 of 6	NP_001371262.1	Q4W5P6
	SMIM43	NM_001384334.1		c.*291G>T		3_prime_UTR	Exon 4 of 5	NP_001371263.1	Q4W5P6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMIM43	ENST00000643802.2	MANE Select	c.*291G>T		3_prime_UTR	Exon 4 of 6	ENSP00000495721.1	Q4W5P6
	SMIM43	ENST00000643663.2		c.*406G>T		3_prime_UTR	Exon 5 of 7	ENSP00000495936.2	Q4W5P6
	SMIM43	ENST00000394394.5	TSL:3	n.434G>T		non_coding_transcript_exon	Exon 4 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000409 AC: 1 AN: 244576 AF XY: 0.00000758

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000309

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1454942 Hom.: 0 Cov.: 32 AF XY: 0.00000415 AC XY: 3 AN XY: 723424

African (AFR) AF: 0.0000301 AC: 1 AN: 33186

American (AMR) AF: 0.0000232 AC: 1 AN: 43062

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26016

East Asian (EAS) AF: 0.00 AC: 0 AN: 39494

South Asian (SAS) AF: 0.00 AC: 0 AN: 84104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1109734

Other (OTH) AF: 0.00 AC: 0 AN: 60200

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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	0.090
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.2
DANN	Benign	0.48
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.47
PrimateAI	Benign	0.31	T
Polyphen		0.0010	B
MutPred		0.22		Gain of loop (P = 0.0097)
ClinPred		0.019	T
GERP RS		1.2
Varity_R		0.039
gMVP		0.0093

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs780379584; hg19: chr4-122683035;