rs10853283

Variant names:

• chr18-2715729-T-C
• rs10853283
• NM_015295.3:c.2261-2429T>C

Variant summary

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

The NM_015295.3(SMCHD1):​c.2261-2429T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,016 control chromosomes in the GnomAD database, including 6,839 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (6839 hom., cov: 31)
• Consequence: SMCHD1 NM_015295.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 2 publications found

Genes affected

SMCHD1 (HGNC:29090): (structural maintenance of chromosomes flexible hinge domain containing 1) This gene encodes a protein which contains a hinge region domain found in members of the SMC (structural maintenance of chromosomes) protein family. [provided by RefSeq, Dec 2011]

SMCHD1 Gene-Disease associations (from GenCC):

• arhinia, choanal atresia, and microphthalmia

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Ambry Genetics, ClinGen, Illumina
• facioscapulohumeral muscular dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hyposmia-nasal and ocular hypoplasia-hypogonadotropic hypogonadism syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000266049 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015295.3. 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
	SMCHD1	NM_015295.3	MANE Select	c.2261-2429T>C		intron	N/A	NP_056110.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMCHD1	ENST00000320876.11	TSL:5 MANE Select	c.2261-2429T>C		intron	N/A	ENSP00000326603.7
	SMCHD1	ENST00000688342.1		c.2261-2429T>C		intron	N/A	ENSP00000508422.1
	SMCHD1	ENST00000577880.5	TSL:2	n.674-2429T>C		intron	N/A	ENSP00000463049.1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44728 AN: 151898 Hom.: 6823 Cov.: 31

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.299

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.295 AC: 44776 AN: 152016 Hom.: 6839 Cov.: 31 AF XY: 0.297 AC XY: 22050 AN XY: 74300

African (AFR) AF: 0.248 AC: 10264 AN: 41432

American (AMR) AF: 0.359 AC: 5489 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1183 AN: 3470

East Asian (EAS) AF: 0.497 AC: 2558 AN: 5148

South Asian (SAS) AF: 0.448 AC: 2159 AN: 4814

European-Finnish (FIN) AF: 0.267 AC: 2817 AN: 10568

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19180 AN: 67982

Other (OTH) AF: 0.302 AC: 638 AN: 2112

Alfa AF: 0.287 Hom.: 825

Bravo AF: 0.304

Asia WGS AF: 0.491 AC: 1707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.87
DANN	Benign	0.26
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs10853283; hg19: chr18-2715727;