Genetic Variant GHITM:c.-42G>T (chr10-84139591-G-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

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

Publications

7 publications found

Variant links:

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]

GHITM links:

ENSG00000271933 (HGNC:):

ENSG00000271933 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014394.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GHITM	NM_014394.3	MANE Select	c.-42G>T		splice_region	Exon 1 of 9	NP_055209.2
	GHITM	NM_014394.3	MANE Select	c.-42G>T		5_prime_UTR	Exon 1 of 9	NP_055209.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GHITM	ENST00000372134.6	TSL:1 MANE Select	c.-42G>T	splice_region	Exon 1 of 9	ENSP00000361207.3
GHITM	ENST00000372134.6	TSL:1 MANE Select	c.-42G>T	5_prime_UTR	Exon 1 of 9	ENSP00000361207.3
GHITM	ENST00000686583.1		c.-180G>T	splice_region	Exon 1 of 10	ENSP00000510236.1

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18520

AN:

152170

Hom.:

2437

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.0833

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0857

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.122

AC:

18554

AN:

152288

Hom.:

2446

Cov.:

AF XY:

0.116

AC XY:

8638

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.331

AC:

13736

AN:

41530

American (AMR)

AF:

0.0662

AC:

1014

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0409

AC:

142

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.0104

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0166

AC:

176

AN:

10624

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0452

AC:

3074

AN:

68014

Other (OTH)

AF:

0.0998

AC:

211

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

727

1455

2182

2910

3637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0935

Hom.:

498

Bravo

AF:

0.135

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.72

PhyloP100

1.0

PromoterAI

-0.25

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over