18-75427380-C-G

Variant names:

• chr18-75427380-C-G
• rs7235563
• NM_001037331.3:c.129+55G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001037331.3(SMIM21):​c.129+55G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,580,254 control chromosomes in the GnomAD database, including 92,763 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (6718 hom., cov: 32)
  • Exomes 𝑓: 0.34 (86045 hom.)
• Consequence: SMIM21 NM_001037331.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790
• Publications: 10 publications found

Genes affected

SMIM21 (HGNC:27598): (small integral membrane protein 21) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037331.3. 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
	SMIM21	NM_001037331.3	MANE Select	c.129+55G>C		intron	N/A	NP_001032408.1	Q3B7S5
	SMIM21	NM_001303482.2		c.129+55G>C		intron	N/A	NP_001290411.1	J3KSN8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMIM21	ENST00000579022.5	TSL:1 MANE Select	c.129+55G>C		intron	N/A	ENSP00000462106.1	Q3B7S5
	SMIM21	ENST00000584508.1	TSL:1	c.129+55G>C		intron	N/A	ENSP00000462572.1	J3KSN8
	SMIM21	ENST00000382638.3	TSL:1	c.129+55G>C		intron	N/A	ENSP00000372083.3	J9JIF2

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43052 AN: 151982 Hom.: 6726 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.315

GnomAD4 exome AF: 0.343 AC: 489855 AN: 1428154 Hom.: 86045 AF XY: 0.344 AC XY: 243305 AN XY: 707624

African (AFR) AF: 0.143 AC: 4734 AN: 33058

American (AMR) AF: 0.213 AC: 9224 AN: 43326

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 10309 AN: 24108

East Asian (EAS) AF: 0.243 AC: 9557 AN: 39330

South Asian (SAS) AF: 0.301 AC: 23880 AN: 79392

European-Finnish (FIN) AF: 0.378 AC: 19471 AN: 51500

Middle Eastern (MID) AF: 0.357 AC: 2009 AN: 5628

European-Non Finnish (NFE) AF: 0.358 AC: 390855 AN: 1092750

Other (OTH) AF: 0.336 AC: 19816 AN: 59062

GnomAD4 genome AF: 0.283 AC: 43041 AN: 152100 Hom.: 6718 Cov.: 32 AF XY: 0.282 AC XY: 21003 AN XY: 74372

African (AFR) AF: 0.148 AC: 6121 AN: 41486

American (AMR) AF: 0.240 AC: 3660 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1469 AN: 3470

East Asian (EAS) AF: 0.197 AC: 1023 AN: 5184

South Asian (SAS) AF: 0.284 AC: 1368 AN: 4822

European-Finnish (FIN) AF: 0.377 AC: 3987 AN: 10584

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24419 AN: 67970

Other (OTH) AF: 0.315 AC: 665 AN: 2110

Alfa AF: 0.207 Hom.: 485

Bravo AF: 0.263

Asia WGS AF: 0.252 AC: 877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.4
DANN	Benign	0.50
PhyloP100		-0.079
PromoterAI		0.016	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs7235563; hg19: chr18-73139335; COSMIC: COSV66894556;