NM_014394.3:c.326C>T

Variant names:

• chr10-84144091-C-T
• rs747348841
• NM_014394.3:c.326C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014394.3(GHITM):​c.326C>T​(p.Ala109Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A109G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GHITM NM_014394.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.48
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.746

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GHITM	NM_014394.3	MANE Select	c.326C>T	p.Ala109Val	missense	Exon 4 of 9	NP_055209.2	Q9H3K2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GHITM	ENST00000372134.6	TSL:1 MANE Select	c.326C>T	p.Ala109Val	missense	Exon 4 of 9	ENSP00000361207.3	Q9H3K2
	GHITM	ENST00000897422.1		c.326C>T	p.Ala109Val	missense	Exon 4 of 9	ENSP00000567481.1
	GHITM	ENST00000686247.1		c.326C>T	p.Ala109Val	missense	Exon 5 of 10	ENSP00000509112.1	Q9H3K2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1455816 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 724794

African (AFR) AF: 0.00 AC: 0 AN: 33366

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.00 AC: 0 AN: 86150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106466

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

GnomAD4 genome Cov.: 33

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.30
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.073	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0049	T
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		7.5
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.29
Sift	Benign	0.14	T
Sift4G	Benign	0.60	T
Polyphen		0.95	P
Vest4		0.69
MutPred		0.41		Gain of sheet (P = 0.0036)
MVP		0.48
MPC		0.20
ClinPred		0.86	D
GERP RS		6.2
Varity_R		0.14
gMVP		0.89
Mutation Taster		=61/39	polymorphism

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: rs747348841; hg19: chr10-85903847;