X-53422619-G-T

Variant names:

• chrX-53422619-G-T
• rs1264011
• NM_006306.4:c.-19C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006306.4(SMC1A):​c.-19C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000002 in 1,002,188 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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: not found (cov: 25)
  • Exomes 𝑓: 0.0000020 (0 hom. 0 hem.)
• Consequence: SMC1A NM_006306.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251
• Publications: 0 publications found

Genes affected

SMC1A (HGNC:11111): (structural maintenance of chromosomes 1A) Proper cohesion of sister chromatids is a prerequisite for the correct segregation of chromosomes during cell division. The cohesin multiprotein complex is required for sister chromatid cohesion. This complex is composed partly of two structural maintenance of chromosomes (SMC) proteins, SMC3 and either SMC1B or the protein encoded by this gene. Most of the cohesin complexes dissociate from the chromosomes before mitosis, although those complexes at the kinetochore remain. Therefore, the encoded protein is thought to be an important part of functional kinetochores. In addition, this protein interacts with BRCA1 and is phosphorylated by ATM, indicating a potential role for this protein in DNA repair. This gene, which belongs to the SMC gene family, is located in an area of the X-chromosome that escapes X inactivation. Mutations in this gene result in Cornelia de Lange syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

RIBC1 (HGNC:26537): (RIB43A domain with coiled-coils 1)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006306.4. 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
	SMC1A	NM_006306.4	MANE Select	c.-19C>A		5_prime_UTR	Exon 1 of 25	NP_006297.2
	SMC1A	NM_001281463.1		c.-231C>A		5_prime_UTR	Exon 1 of 26	NP_001268392.1	G8JLG1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMC1A	ENST00000322213.9	TSL:1 MANE Select	c.-19C>A		5_prime_UTR	Exon 1 of 25	ENSP00000323421.3	Q14683
	SMC1A	ENST00000375340.10	TSL:1	c.-231C>A		5_prime_UTR	Exon 1 of 26	ENSP00000364489.7	G8JLG1
	RIBC1	ENST00000929472.1		c.-128G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	ENSP00000599531.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.00000200 AC: 2 AN: 1002188 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 293436

African (AFR) AF: 0.00 AC: 0 AN: 24084

American (AMR) AF: 0.00 AC: 0 AN: 34935

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18725

East Asian (EAS) AF: 0.00 AC: 0 AN: 29631

South Asian (SAS) AF: 0.00 AC: 0 AN: 51866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39383

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3933

European-Non Finnish (NFE) AF: 0.00000132 AC: 1 AN: 756790

Other (OTH) AF: 0.0000233 AC: 1 AN: 42841

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.7
DANN	Benign	0.90
PhyloP100		0.25
PromoterAI		-0.042	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.1

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: rs1264011; hg19: chrX-53449568;