rs1136944

Variant names:

• chr10-84139591-G-T
• rs1136944
• NM_014394.3:c.-42G>T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_014394.3(GHITM):​c.-42G>T variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,376 control chromosomes in the GnomAD database, including 2,446 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (2446 hom., cov: 33)
  • Exomes 𝑓: 0.080 (0 hom.)
• Consequence: GHITM NM_014394.3 splice_region
• Scores: Splicing: ADA: 0.008354
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

Genes affected

GHITM (HGNC:17281): (growth hormone inducible transmembrane protein) Involved in inner mitochondrial membrane organization and negative regulation of release of cytochrome c from mitochondria. Located in mitochondrion. Is integral component of mitochondrial inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000271933 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GHITM	NM_014394.3	c.-42G>T		splice_region_variant	Exon 1 of 9	ENST00000372134.6	NP_055209.2
GHITM	NM_014394.3	c.-42G>T		5_prime_UTR_variant	Exon 1 of 9	ENST00000372134.6	NP_055209.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GHITM	ENST00000372134.6	c.-42G>T		splice_region_variant	Exon 1 of 9	1	NM_014394.3	ENSP00000361207.3
GHITM	ENST00000372134	c.-42G>T		5_prime_UTR_variant	Exon 1 of 9	1	NM_014394.3	ENSP00000361207.3

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18520 AN: 152170 Hom.: 2437 Cov.: 33

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.0663

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.0166

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0452

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.0795 AC: 7 AN: 88 Hom.: 0 Cov.: 0 AF XY: 0.0833 AC XY: 6 AN XY: 72

Gnomad4 AFR exome AF: 0.250

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0857

GnomAD4 genome AF: 0.122 AC: 18554 AN: 152288 Hom.: 2446 Cov.: 33 AF XY: 0.116 AC XY: 8638 AN XY: 74486

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.0662

Gnomad4 ASJ AF: 0.0409

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0104

Gnomad4 FIN AF: 0.0166

Gnomad4 NFE AF: 0.0452

Gnomad4 OTH AF: 0.0998

Alfa AF: 0.0885 Hom.: 372

Bravo AF: 0.135

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	16
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0084
dbscSNV1_RF	Benign	0.16
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1136944; hg19: chr10-85899347; COSMIC: COSV64538335;