11-77590127-C-T

Variant names:

• chr11-77590127-C-T
• rs2135741696
• NM_173039.3:c.135C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6 BP7

The NM_173039.3(AQP11):​c.135C>T​(p.His45His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AQP11 NM_173039.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0800
• Publications: 0 publications found

Genes affected

AQP11 (HGNC:19940): (aquaporin 11) Enables glycerol channel activity and water channel activity. Involved in several processes, including glycerol transport; hydrogen peroxide transmembrane transport; and protein homooligomerization. Located in cell surface; endoplasmic reticulum; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CLNS1A (HGNC:2080): (chloride nucleotide-sensitive channel 1A) This gene encodes a protein that functions in multiple regulatory pathways. The encoded protein complexes with numerous cytosolic proteins and performs diverse functions including regulation of small nuclear ribonucleoprotein biosynthesis, platelet activation and cytoskeletal organization. The protein is also found associated with the plasma membrane where it functions as a chloride current regulator. Pseudogenes of this gene are found on chromosomes 1, 4 and 6. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 11-77590127-C-T is Benign according to our data. Variant chr11-77590127-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2681316.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.08 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173039.3. 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
	AQP11	NM_173039.3	MANE Select	c.135C>T	p.His45His	synonymous	Exon 1 of 3	NP_766627.1	Q8NBQ7
	AQP11	NM_001363477.2		c.135C>T	p.His45His	synonymous	Exon 1 of 2	NP_001350406.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP11	ENST00000313578.4	TSL:1 MANE Select	c.135C>T	p.His45His	synonymous	Exon 1 of 3	ENSP00000318770.3	Q8NBQ7
	AQP11	ENST00000528638.1	TSL:1	n.291-402C>T		intron	N/A
	AQP11	ENST00000925651.1		c.135C>T	p.His45His	synonymous	Exon 1 of 3	ENSP00000595710.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1455798 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724364

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47906

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111766

Other (OTH) AF: 0.00 AC: 0 AN: 60324

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	EBV-positive nodal T- and NK-cell lymphoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	9.5
DANN	Benign	0.93
PhyloP100		0.080
PromoterAI		0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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: rs2135741696; hg19: chr11-77301172;