rs6622126

Variant names:

• chrX-106956972-G-A
• rs6622126
• NM_024657.5:c.1418C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024657.5(MORC4):​c.1418C>T​(p.Thr473Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 1,085,475 control chromosomes in the GnomAD database, including 89,810 homozygotes. There are 170,576 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 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: 𝑓 0.58 (14348 hom., 19204 hem., cov: 23)
  • Exomes 𝑓: 0.48 (89810 hom. 170576 hem.)
  • Failed GnomAD Quality Control
• Consequence: MORC4 NM_024657.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.575
• Publications: 42 publications found

Genes affected

MORC4 (HGNC:23485): (MORC family CW-type zinc finger 4) In human, the four current members of the microrchidia (morc) gene family share an N-terminal ATPase-like ATP-binding region and a CW four-cysteine zinc-finger motif. The protein encoded by this gene also has a nuclear matrix binding domain and a two-stranded coiled-coil motif near its C-terminus. This gene is widely expressed at low levels in normal tissues and has elevated expression in placenta and testis. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jan 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.3747166E-6).
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024657.5. 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
	MORC4	NM_024657.5	MANE Select	c.1418C>T	p.Thr473Ile	missense	Exon 12 of 17	NP_078933.3
	MORC4	NM_001085354.3		c.1418C>T	p.Thr473Ile	missense	Exon 12 of 17	NP_001078823.1	Q8TE76-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MORC4	ENST00000355610.9	TSL:1 MANE Select	c.1418C>T	p.Thr473Ile	missense	Exon 12 of 17	ENSP00000347821.4	Q8TE76-1
	MORC4	ENST00000255495.7	TSL:1	c.1418C>T	p.Thr473Ile	missense	Exon 12 of 17	ENSP00000255495.7	Q8TE76-3
	MORC4	ENST00000966192.1		c.1418C>T	p.Thr473Ile	missense	Exon 12 of 18	ENSP00000636251.1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 63887 AN: 110789 Hom.: 14349 Cov.: 23

Gnomad AFR AF: 0.814

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.563

GnomAD2 exomes AF: 0.576 AC: 104789 AN: 181992 AF XY: 0.558

Gnomad AFR exome AF: 0.820

Gnomad AMR exome AF: 0.795

Gnomad ASJ exome AF: 0.467

Gnomad EAS exome AF: 0.935

Gnomad FIN exome AF: 0.406

Gnomad NFE exome AF: 0.417

Gnomad OTH exome AF: 0.508

GnomAD4 exome AF: 0.478 AC: 519005 AN: 1085475 Hom.: 89810 Cov.: 26 AF XY: 0.481 AC XY: 170576 AN XY: 354373

African (AFR) AF: 0.822 AC: 21524 AN: 26180

American (AMR) AF: 0.782 AC: 27454 AN: 35095

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 9005 AN: 19179

East Asian (EAS) AF: 0.950 AC: 28557 AN: 30068

South Asian (SAS) AF: 0.704 AC: 37260 AN: 52946

European-Finnish (FIN) AF: 0.406 AC: 16337 AN: 40238

Middle Eastern (MID) AF: 0.441 AC: 1802 AN: 4086

European-Non Finnish (NFE) AF: 0.425 AC: 353954 AN: 832100

Other (OTH) AF: 0.507 AC: 23112 AN: 45583

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.577 AC: 63939 AN: 110839 Hom.: 14348 Cov.: 23 AF XY: 0.580 AC XY: 19204 AN XY: 33107

African (AFR) AF: 0.815 AC: 24817 AN: 30464

American (AMR) AF: 0.671 AC: 7036 AN: 10491

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1226 AN: 2633

East Asian (EAS) AF: 0.926 AC: 3234 AN: 3494

South Asian (SAS) AF: 0.712 AC: 1866 AN: 2620

European-Finnish (FIN) AF: 0.404 AC: 2385 AN: 5909

Middle Eastern (MID) AF: 0.361 AC: 78 AN: 216

European-Non Finnish (NFE) AF: 0.422 AC: 22297 AN: 52828

Other (OTH) AF: 0.567 AC: 852 AN: 1503

Alfa AF: 0.484 Hom.: 70675

Bravo AF: 0.610

TwinsUK AF: 0.427 AC: 1584

ALSPAC AF: 0.433 AC: 1250

ESP6500AA AF: 0.813 AC: 3119

ESP6500EA AF: 0.430 AC: 2890

ExAC AF: 0.566 AC: 68696

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-1.0	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.013
DANN	Benign	0.39
DEOGEN2	Benign	0.014	T
FATHMM_MKL	Benign	0.0036	N
LIST_S2	Benign	0.047	T
MetaRNN	Benign	0.0000014	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.3	N
PhyloP100		-0.57
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.033
Sift	Benign	1.0	T
Sift4G	Benign	0.19	T
Polyphen		0.0	B
Vest4		0.016
MPC		0.37
ClinPred		0.0028	T
GERP RS		-3.7
Varity_R		0.037
gMVP		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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: rs6622126; hg19: chrX-106200202; COSMIC: COSV55245815;