rs754005624

Variant names:

• chrX-54749995-T-A
• rs754005624
• NM_198510.3:c.3842A>T

Your query was ambiguous. Multiple possible variants found:

• chrX-54749995-T-A
• chrX-54749995-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_198510.3(ITIH6):​c.3842A>T​(p.Asp1281Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000455 in 1,097,784 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000046 (0 hom. 3 hem.)
• Consequence: ITIH6 NM_198510.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87

Genes affected

ITIH6 (HGNC:28907): (inter-alpha-trypsin inhibitor heavy chain family member 6) The protein encoded by this gene belongs to the interalpha trypsin inhibitor heavy chain (ITIH) family. Interalpha trypsin inhibitor (ITI) is composed of two heavy chains (containing VWA domain) and one light chain. The light chain confers the protease-inhibitor function, while the heavy chains are involved in mediating protein-protein interactions with the components of the extracellular matrix. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14651904).
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITIH6	NM_198510.3	c.3842A>T	p.Asp1281Val	missense_variant	Exon 13 of 13	ENST00000218436.7	NP_940912.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITIH6	ENST00000218436.7	c.3842A>T	p.Asp1281Val	missense_variant	Exon 13 of 13	1	NM_198510.3	ENSP00000218436.6

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD3 exomes AF: 0.0000219 AC: 4 AN: 182890 Hom.: 0 AF XY: 0.0000297 AC XY: 2 AN XY: 67400

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000526

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000368

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000455 AC: 5 AN: 1097784 Hom.: 0 Cov.: 30 AF XY: 0.00000826 AC XY: 3 AN XY: 363148

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000475

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

Alfa AF: 0.0000434 Hom.: 0

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.000109

EpiControl AF: 0.000238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0032	T
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.16
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.95	P
Vest4		0.076
MutPred		0.49		Loss of helix (P = 0.0138);
MVP		0.18
MPC		0.018
ClinPred		0.49	T
GERP RS		2.3
Varity_R		0.41
gMVP		0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs754005624; hg19: chrX-54776428;