9-35906393-C-T

Variant names:

• chr9-35906393-C-T
• rs143621211
• NM_001039792.2:c.106C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001039792.2(HRCT1):​c.106C>T​(p.Arg36Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000428 in 1,612,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R36Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: HRCT1 NM_001039792.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.354
• Publications: 2 publications found

Genes affected

HRCT1 (HGNC:33872): (histidine rich carboxyl terminus 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09838298).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039792.2. 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
	HRCT1	NM_001039792.2	MANE Select	c.106C>T	p.Arg36Trp	missense	Exon 1 of 1	NP_001034881.1	Q6UXD1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRCT1	ENST00000354323.3	TSL:6 MANE Select	c.106C>T	p.Arg36Trp	missense	Exon 1 of 1	ENSP00000346283.2	Q6UXD1

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 20 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000485 AC: 12 AN: 247422 AF XY: 0.0000223

Gnomad AFR exome AF: 0.000252

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000449

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000336 AC: 49 AN: 1460270 Hom.: 0 Cov.: 44 AF XY: 0.0000289 AC XY: 21 AN XY: 726530

African (AFR) AF: 0.000448 AC: 15 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39694

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51914

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000225 AC: 25 AN: 1111972

Other (OTH) AF: 0.0000663 AC: 4 AN: 60360

GnomAD4 genome AF: 0.000131 AC: 20 AN: 152184 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74350

African (AFR) AF: 0.000434 AC: 18 AN: 41446

American (AMR) AF: 0.000131 AC: 2 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000119 Hom.: 0

Bravo AF: 0.000170

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000495 AC: 6

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.35
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.063
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.029	D
Polyphen		1.0	D
Vest4		0.31
MVP		0.13
MPC		0.17
ClinPred		0.67	D
GERP RS		-0.20
PromoterAI		-0.049	Neutral
Varity_R		0.12
gMVP		0.11
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs143621211; hg19: chr9-35906390;